At last, 'dud hormone' gets to the heart of its value

Date: November 08 2012

Bridie Smith

IT TOOK five clinical trials, collaboration with six different biotechnology companies and almost four decades of study. But finally the obscure hormone to which chemist Geoff Tregear dedicated his research career has come through with the goods.

No longer will it be dismissed as "the dud hormone". As of today a synthetic version of relaxin — a hormone first described in 1929 — is the key ingredient in a new class of medicine for acute heart failure that has been shown to improve symptoms and reduce deaths among sufferers.

Now retired, Professor Tregear, 71, began his relaxin research in Melbourne in 1975. And while he knew the hormone was important, it took decades to prove it.

"There was always people asking 'why are we still working on relaxin, it doesn't do anything'," he said.

With patience and perseverance, Professor Tregear and his Howard Florey Institute colleagues set about establishing the chemistry and biology of relaxin, a member of the insulin family. They were the first to isolate the genes that code relaxin and the first to make it artificially, allowing scientists to explore its potential therapeutic uses.

"It's a fascinating molecule. Everything about it is unusual and unexpected," he said.

Among the bigger surprises was when it was expressed in humans. In all other mammals relaxin is produced at the end of pregnancy, just prior to delivery. But in humans it is found in the bloodstream in the early stages of pregnancy.

Made in the ovaries, the hormone is critical for the maintenance of pregnancy because it has a positive effect on the heart, vascular system and kidney function. Professor Tregear said the hormone is also found in semen — and it may mean it enhances sperm movement.

"In the human relaxin is playing this really critical role in the early stages of life and now we are using it pharmacologically at the other end of life where your heart is failing because you're getting too old," he said.

He said there was potential for treatment of other conditions because relaxin breaks down scar tissue and this ability could be applied to damaged organs such as the lungs and kidneys.

Phase three trial results of the Novartis drug, outlined in The Lancet on Wednesday, showed the drug improved symptoms and reduced deaths in patients with acute heart failure by one-third after six months.

According to the Heart Foundation at least 300,000 Australians suffer from heart failure, with an estimated 30,000 Australians diagnosed with chronic heart failure each year. It kills about 2900 people a year, almost 60 per cent of whom are women.

The foundation's chief medical adviser Professor James Tatoulis said the drug had the potential to be used to supplement current heart failure treatments.

This material is subject to copyright and any unauthorised use, copying or mirroring is prohibited.